Mucinous carcinoma originating from uterine adenomyosis: a case report

Background Uterine adenomyosis is rarely a precursor of malignant tumors, but the most frequent histologi- cal subtype is endometrioid carcinoma. We observed a rare case of mucinous carcinoma originating from uterine adenomyosis. Case presentation A 63-year-old Japanese woman presented to our hospital with lower abdominal pain. She had no atypical genital bleeding. Ultrasound demonstrated thickening of the entire uterine wall, but the endometrium was not thick. Magnetic resonance imaging demonstrated an enlarged uterus with thickening of the entire uterine wall, suggesting adenomyosis. On the basis of the specimen of endocervical curettage, adenocarcinoma originating from the endometrium was suspected. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed to confirm the diagnosis. Macroscopically, the resected enlarged uterus had no nodules and exudation of mucin was observed from the cut surface of the thickened myometrium. The surface of the endometrium was smooth. On histological examination, mucinous carcinoma invaded almost the entire myometrium. Adenomyotic lesions were distributed focally in the uterine wall, and transition from adenomyotic glandular epithelium to muci- nous carcinoma was detected within several foci. Although adenocarcinoma cells proliferated adjacent to the endo- metrium, the primary endometrial epithelium was atrophic without atypia. Throughout the myometrium, the muci- nous carcinoma cells proliferated and floated in dilated lymph vessels with abundant mucin pools. We diagnosed this case as mucinous carcinoma originating from adenomyosis. Although the patient received 11 courses of intravenous adjuvant chemotherapy, she died of disease 18 months after the first operation.

As only one case of mucinous carcinoma originating from adenomyosis has been reported to date, this is the second case report of mucinous carcinoma. Moreover, an abnormal manner of proliferation with marked lym- phatic permeation of the tumor cells throughout the myometrium was observed.

Mucinous carcinoma, Adenomyosis, Case report

The ovary is the most common site of endometriosis, and endometriosis-associated ovarian cancer accounts for 0.3–1.0% of endometriosis [1]. The histological types of endometriosis-associated ovarian cancers are predomi - nantly endometrioid and clear cell carcinoma, whereas serous and mucinous carcinoma are rare [2]. Uterine adenomyosis, a type of extraovarian endometriosis, is rarely a precursor of malignant tumor, but the most fre - quent histological subtype is endometrioid carcinoma [3]. We report a rare case of mucinous carcinoma originating *Correspondence: Satoshi Ohira [email protected] 1 Department of Obstetrics and Gynecology, Iida Municipal Hospital, 438 Yawatamachi, Iida 395-8502, Japan 2 Department of Pathology, Iida Municipal Hospital, 438 Yawatamachi, Iida 395-8502, Japan Page 2 of 5Ohira et al. Journal of Medical Case Reports (2023) 17:36 from uterine adenomyosis. The current case exhibited an abnormal manner of proliferation with marked lymphatic permeation of the tumor cells throughout the myome - trium, and this abnormal manner has not been reported to our knowledge. Case presentation A 63-year-old postmenopausal Japanese woman (gravida 2, para 2) presented to the internal medicine of our hos - pital with a 2-month history of lower abdominal pain. Although uterine adenomyosis was noted in her forties, it was not followed up. She had no atypical genital bleed - ing. As the serum carbohydrate antigen 19-9 (CA19-9) level was high at 64,868  U/mL, close inspection of the pancreas, gallbladder, liver, and gastrointestinal tract was performed. Although gallbladder adenomyomatosis was detected, no malignant diseases were observed in these organs. Abdominal computed tomography (CT) revealed an enlarged uterus; therefore, she was referred to the department of gynecology. Ultrasound demonstrated thickening of the entire uterine wall, but the endome - trium was not thick. Cytological testing of the endocer - vix revealed atypical glandular cells. Although it was not possible to pass the probe beyond the cervix, owing to the specimen of endocervical curettage, adenocarci - noma originating from the endometrium was suspected. Magnetic resonance imaging (MRI) demonstrated an enlarged uterus with thickening of the entire uterine wall, suggesting adenomyosis. Both T1- and T2-weighted imaging revealed no uterine nodules (Fig. 1). Three weeks later from the measurement with internal medicine, the serum CA19-9 level was markedly high at 115,950 U/mL. The serum cancer antigen 125 (CA125) level was high at 113.7 U/mL, whereas the carcinoembryonic antigen level was normal. No metastatic lesions were found on chest and abdominal CT. Total abdominal hysterectomy and bilateral salpingo- oophorectomy were performed to confirm the diagno - sis. Intraoperative ascitic cytology was negative, and there was no peritoneal dissemination. Macroscopically, the resected enlarged uterus had no nodules and exuda - tion of mucin was observed from the cut surface of the thickened myometrium. The surface of the endometrium was smooth, and the bilateral ovaries were unremarkable (Fig. 2). On histological examination, mucinous carcinoma (not otherwise specified; NOS) invaded almost the entire myometrium (Fig.  3a). The tumor cells had a cribriform pattern composed of mucin-producing columnar epithe - lium. The nuclei of the tumor cells were hyperchromatic; mitotic figures were sporadically observed. Adenomy - otic lesions were distributed focally in the uterine wall, Fig. 1 Magnetic resonance imaging demonstrated an enlarged uterus with thickening of the entire uterine wall, suggesting adenomyosis. Both T1-weighted (a) and T2-weighted (b) imaging revealed no uterine nodules Page 3 of 5 Ohira et al. Journal of Medical Case Reports (2023) 17:36 and transition from adenomyotic glandular epithelium to mucinous carcinoma was detected within several foci (Fig.  3b). Although adenocarcinoma cells prolifer - ated adjacent to the endometrium, the primary endo - metrial epithelium was atrophic without atypia (Fig.  3c). Throughout the myometrium, the mucinous carcinoma cells proliferated and floated in dilated lymph vessels with abundant mucin pools (Fig.  3d). Microscopic meta - static lesions were observed in both ovaries. Endocervi - cal epithelium and stroma of the uterine cervix were free of malignancy. Immunohistochemically, the adenocarci - noma cells were positive for p53 and CA19-9, but nega - tive for estrogen receptor and p16. According to the International Federation of Gynecol - ogy and Obstetrics (FIGO 2008) staging, we diagnosed this case as stage IIIA mucinous carcinoma originating from adenomyosis, pT3aN0MX. The patient received intravenous adjuvant chemotherapy (paclitaxel 175  mg/ m2 and carboplatin AUC6). After six courses of chemo - therapy, the serum CA19-9 and CA125 levels decreased to 36 U/mL and 7.4 U/mL, respectively. Three months after the last course of chemotherapy, the serum CA19-9 level increased to 455  U/mL, and pelvic CT revealed swelling of left common iliac lymph node. Although the progressive disease was noted, the patient underwent five more courses of intravenous chemotherapy (paclitaxel 175  mg/m 2 and carboplatin AUC6) in consideration of the patient’s desire. However, the degree of swelling of the lymph node on CT did not decrease and the left pelvic lymph nodes were resected. Fig. 2 Macroscopically, the resected enlarged uterus had no nodules and the surface of the endometrium was smooth Fig. 3 Histological findings of the resected uterus (hematoxylin and eosin staining). a Mucinous carcinoma invaded the myometrium and the tumor cells had a cribriform pattern composed of mucin-producing columnar epithelium. b Adenomyotic lesions were distributed focally in the uterine wall, and the transition from adenomyotic glandular epithelium to mucinous carcinoma was detected within several foci. c Although adenocarcinoma cells proliferated adjacent to the endometrium, the primary endometrial epithelium was atrophic without atypia. d The mucinous carcinoma cells proliferated and floated in dilated lymph vessels with abundant mucin pools Page 4 of 5Ohira et al. Journal of Medical Case Reports (2023) 17:36 Microscopically, metastasis of adenocarcinoma was observed in the left common iliac lymph nodes. After a month of the second operation, CT revealed large swell - ing of paraaortic and mediastinal lymph nodes. The patient died of disease 18 months after the first operation.

Malignant neoplasms originating from uterine adenomy - osis are rare. Koshiyama et al. reported that adenocarci - noma originating from adenomyosis accounted for 0.7% of all uterine body carcinomas treated by hysterectomy [4]. The most frequent histological subtype of malignant lesions is endometrioid carcinoma [3]. In our literature review, we found 23 well-documented cases of other histological subtypes as follows: 4 clear cell carcinomas [3–6], 4 serous carcinomas [4, 7, 8], 6 serous endome - trial intraepithelial carcinomas [8, 9], 6 adenosarcomas [10–15], and 1 case each of adenosquamous carcinoma [16], carcinosarcoma [17], and mucinous carcinoma (minimal deviation adenocarcinoma; MDA) [18]. There - fore, the current case is the second case of mucinous car - cinoma originating from uterine adenomyosis. Moreover, the current case (mucinous carcinoma, NOS) is distin - guished from the reported case of mucinous carcinoma, gastric type (MDA). The diagnostic criteria for carcinoma developing from adenomyosis were proposed by Colman and Rosenthal as follows [19]: (i) the carcinoma should be absent from the endometrium and elsewhere in the pelvis; (ii) the car- cinoma should be observed arising from the epithelium of the areas of adenomyosis and not invading it from another source; and (iii) endometrial stromal cells should be surrounding the aberrant glands to support the diag - nosis of adenomyosis. Our case does not strictly meet Colman’s criteria because the specimen of preoperative endocervical curettage suggested adenocarcinoma origi - nating from the endometrium. However, we consider the diagnosis consistent with that of mucinous carcinoma originating from adenomyosis because of the observ - able transitions between adenomyosis and mucinous carcinoma. In the current case, the tumor cells exhibited an abnor - mal manner of proliferation, that is, the mucinous car - cinoma cells diffusely proliferated and floated in dilated lymph vessels with abundant mucin pools throughout the myometrium. Demarcated nodules were not observed on preoperative MRI or included in macroscopic findings of the resected uterus. Many cases of malignant tumors origi- nating from adenomyosis exhibited demarcated lesions in the myometrium [6 , 7, 15, 17, 20], and abnormal pro - liferation, as observed in our case, has not been reported to our knowledge. Moreover, the preoperative serum CA19-9 level in our case was markedly high at 115,950 U/ mL. One reason for the high serum CA19-9 level was the marked mucin production from carcinoma cells. Although our patient underwent intravenous chemotherapy for the recurrent tumor in the pelvis, the treatment option might be radiotherapy in a case of recurrent mucinous carcinoma [21]. The prognosis of endometrial carcinoma originating from adenomyosis remains controversial. Machida et  al. described that endometrial carcinoma arising in adenomy- osis (EC-AIA) group (n = 46) had a significantly decreased 5-year disease-free survival (DFS) rates compared with endometrial cancer coexisting with adenomyosis (EC-A) group (n = 350) (72.2% versus 85.5%, p = 0.001) [22]. Mean- while, Chao et  al. studied a population with endometrial endometrioid carcinoma and described that the 5-year DFS rates were 96% in the group of EC without adenomyo- sis (n = 1043), 91% in the EC-A group (n = 230), and 100% in the EC-AIA group (n = 28) (p = 0.045) [23].

We described a rare case of mucinous carcinoma originat- ing from uterine adenomyosis. This case demonstrated an abnormal manner of proliferation with marked lymphatic permeation of the tumor cells throughout the myome - trium. Further accumulation of cases is needed to clarify the pathogenesis and behavior of mucinous carcinoma originating from adenomyosis. Abbreviations CA19-9 Carbohydrate antigen 19-9 CT Computed tomography MRI Magnetic resonance imaging CA125 Cancer antigen 125 NOS Not otherwise specified MDA Minimal deviation adenocarcinoma EC-AIA Endometrial carcinoma arising in adenomyosis EC-A Endometrial cancer coexisting with adenomyosis DFS Disease-free survival

The authors are grateful to Tomofumi Watanabe (Department of Radiology, Iida Municipal Hospital) for the radiodiagnosis in this case. Author contributions SO, RT, SY, KT, NU, and EI were in charge of this patient. KS performed histological examination in this case. All authors read and approved the final manuscript. Funding Not applicable. Availability of data and materials All data presented in this report are included in this article. Declarations Ethics approval and consent to participate The study was sent to the ethical committee of Iida Municipal Hospital, and need for approval was waived. Page 5 of 5 Ohira et al. Journal of Medical Case Reports (2023) 17:36 • fast, convenient online submission • thorough peer review by experienced researchers in your field • rapid publication on acceptance • support for research data, including large and complex data types • gold Open Access which fosters wider collaboration and increased citations maximum visibility for your research: over 100M website views per year • At BMC, research is always in progress. Learn more biomedcentral.com/submissions Ready to submit y our researc hReady to submit y our researc h ? Choose BMC and benefit fr om: ? Choose BMC and benefit fr om: Consent for publication Written informed consent was obtained from the patient for publication of this case report. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Competing interests The authors declare that they have no competing interests. Received: 15 February 2022 Accepted: 12 January 2023

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